Research
Sensitive and effective biomarkers that are helpful in timely diagnosis of different diseases are unmet need. Rapid progress in high throughput molecular screening methods and developments in bioinformatics tools in recent years have provided us with new tools in basic and clinical research. Yet current status of availability of effective biomarkers and their use in clinical setting is far from satisfactory. The goal of the Sarwal lab is to identify potentially important diagnostic, prognostic, and therapeutic markers for disease diagnosis, monitoring and therapeutic intervention if necessary. However, discovery of a true biomarker is more efficient with proper understanding of disease mechanism. Therefore, our goal is to unravel the injury causes and mechanisms in diseases. In addition, we aim to discover and validate clinically applicable biomarkers by using powerful state-of-the-art methods and bioinformatics.
Clinical & Translational Research
Cystinosis and impaired autophagy/Mitophagy: Cystinosis is a rare autosomal recessive lysosomal storage disorder caused by the mutations in the CTNS gene encoding the lysosomal membrane transporter cystinosin, resulting in the accumulation of toxic metabolite cysteine in the cells. Continuous cystine accumulation eventually leads to multiorgan dysfunction and in the absence of treatment, they usually develop progressive renal failure by the end of the first decade. Treatment with the drug cysteamine depletes the intracellular cystine and if used early in the
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This is a study about Kidney Function and the effects of COVID. The project is led by an outstanding team of clinicians and researchers across five academic medical/research centers from the University of California system, Rush University, and the University of Michigan. The study will enroll and track 2,000 participants, half have tested positive for COVID-19 and the other half have tested negative. Program Overview With the current situation regarding the SARS-CoV-2 (COVID-19) pandemic, there exists a cloud of “unknown”
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Sensitive and effective biomarkers for different diseases are unmet need. Evolution in high throughput molecular screening methods and developments in bioinformatics tools in recent years have made it possible to conduct comprehensive biomarker discovery efforts in different diseases including organ transplantation. Relentless effort in basic and clinical research have contributed to the identification of potential biomarkers and disease relevant pathways. However, significant work is required before the academic discovery can actually be translated to the patient in the clinic. Integration
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Organ Transplantation Research
GVHD is a clinical problem that has no predictive markers and is a source of high morbidity and mortality for the recipient. Our Lab has used microarrays and QPCR to find a novel gene panel in peripheral blood that can predict the onset of chronic GVHD. These studies are currently being cross-validated in RCT in bone marrow transplants with our collaborators at the Fred Hutchinson Institute and the University of Miami.
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Although recent advances in immunosuppression therapy have enhanced short-term outcome; acute rejection remains an important risk factor for allograft failure. Current management of a transplant patient requires a tissue biopsy as a gold standard for diagnosis, though the process remains limited by sampling error, assessment variability, procedural morbidity and cost. Additionally, renal allograft dysfunction is a relatively insensitive means of detecting early acute rejection such that approximately 10% of patients with clinically normal renal function are found to have evidence
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We are conducting a large-scale genome-wide screening study across injury datasets in organ transplantation, using highly annotated genomic and proteomic datasets in the Sarwal Lab as well as within the public domain. With our expertise in translational bioinformatics to integrate genomic, proteomic, metabolic data from multiple sources, we are developing comprehensive strategy for integrated bioinformatics analysis of archived renal transplant genomic and proteomic datasets available in the Sarwal Lab together with publically available data pertaining to different types of organ
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Chronic allograft injury (CAI) is a poorly understood process of accelerated histological injury in the allograft that results in accelerated functional decline and is the major cause of transplanted kidney loss. We have taken an innovative 3 pronged integrated analysis on serial matched biopsy, urine, and serum samples incorporating biopsy microarrays, urinary proteomics and serum protein-arrays collected from the same kidney transplant patients to discover, validate and predict CAI, before irreversible damage occurs, and eventually replace the invasive renal biopsy
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The Kidney Precision Medicine Project (KPMP) is focused on finding new ways to treat acute kidney injury (AKI) and chronic kidney disease (CKD). We will be obtaining kidney tissues from individuals volunteering to participate in KPMP. The tissue will be analyzed in an effort to redefine kidney disease in molecular terms and identify novel targeted therapies. The network will develop state-of-the-art methods to obtain and analyze these biopsies, linking information on cellular programs with kidney structure. We are also developing
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Urine analysis has a unique advantage in kidney transplantation as it reflects graft injury events that occur in the kidney. Non-invasive urinary biomarker identification, specific and sensitive for graft injury diagnosis and prognosis, would eliminate serial protocol biopsies, advance allograft surveillance, and potentially improve graft survival. While gene based biomarker studies in blood samples are underway in the Sarwal Lab, post-translational modifications of the protein product of the gene may be more critical for determining pathogenesis. With recent advances in
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